Gastroparesis syndrome

　　Primary gastroparesis with secondary characteristics often includes:

　　1. Diabetes;

　　2. Connective tissue diseases, such as progressive systemic sclerosis (PSS);

　　3. Gastric surgery or vagotomy;

　　4. Infection or metabolic abnormalities;

　　5. Central nervous system diseases and certain drugs, etc. In addition, the reduced tone of the vagus nerve and enteric hormones and peptide substances may also play a certain role. In gastroparesis, there may be abnormalities in motilin levels and motilin receptor function.

　　The cause of gastroparesis can be primary gastric motor dysfunction (idiopathic gastroparesis), or secondary to certain systemic diseases and certain gastric surgeries. The mechanism of gastric emptying involves close interaction among gastric smooth muscle, intrinsic or extrinsic enteric nervous system, central nervous system, and hormones. Abnormality in any of these factors can lead to gastroparesis.

　　Secondly, diabetic gastroparesis (DGP)

　　Diabetic patients often have abnormal gastrointestinal motility throughout the entire gastrointestinal tract. In type 1 or type 2 diabetic patients taking oral hypoglycemic drugs, about 40% develop gastroparesis.

　　In 1937, Ferroir observed that X-ray barium meal examination in diabetic patients showed reduced gastric motility. In 1945, Rundles first clearly described the correlation between delayed gastric emptying and diabetes. In 1958, Kassander first applied the term 'diabetic gastroparesis'.

　　Gastroparesis in diabetic patients is characterized by gastrointestinal motility disorders, such as the disappearance of the III phase of migrating motor complex (MMC) in the gastric digestive interval and low postprandial antral motility. The antrum, pylorus, and duodenum exhibit incoordination of contractions and pyloric spasm, leading to delayed gastric emptying of solids. Early in DGP patients, there is dysfunction of proximal gastric compliance and relaxation, resulting in rapid emptying of liquids, but in the late stage, the emptying of gastric liquids is also significantly delayed.

　　The main cause of delayed gastric emptying in DGP patients is vagal nerve injury (autonomic neuropathy), and hyperglycemia also has a suppressive effect on gastric emptying. After diabetes patients are fed or induced hypoglycemia by insulin, the response of gastric acid secretion is reduced, indicating vagal neuropathy. Guy et al. found that the morphological changes of the vagus nerve in diabetic patients are severe reduction in myelinated axon density and thinning of the diameter of the remaining axons. Other studies have not found morphological abnormalities in the gastric wall or abdominal vagus nerve of diabetic patients. No abnormal changes were found in the interstitial nerve plexus of DGP patients. Carbachol and cisapride can stimulate the antrum contraction in DGP patients, suggesting that the antrum smooth muscle function is intact.

　　Third, postoperative gastroparesis

　　Gastroparesis often occurs after gastric surgery. The incidence of delayed gastric emptying after vagotomy is 5% to 10%, and after vagotomy combined with pyloroplasty, it is 28% to 40% for delayed gastric emptying of solid foods. Vagotomy with truncal vagotomy reduces the relaxation function of the gastric fundus, the contraction of the gastric antrum, and the coordinated relaxation function of the pylorus. This leads to accelerated liquid emptying and delayed solid emptying. However, selective (parietal cell) vagotomy can only prolong the delay period of solid emptying without affecting total gastric emptying.

　　About 30% of patients with peptic ulcer and pyloric stenosis who undergo partial gastrectomy and vagotomy develop gastroparesis. For these patients, the measurement of proximal gastric static pressure found that low basal tension of the residual stomach is the main cause of gastric stasis. Patients with Roux-en-Y syndrome also have delayed emptying of the residual stomach. Postoperative gastroparesis can occur in various types of gastric slow wave rhythm abnormalities and the absence of MMC, which are also related to delayed gastric emptying.

　　Fourth, anorexia nervosa

　　About 80% of anorexia nervosa patients have delayed gastric emptying of solid foods, but normal liquid emptying. Delayed gastric emptying is accompanied by gastric antrum motor rhythm disorder, low basal tension of the gastric fundus, decreased plasma norepinephrine and neurotensin concentrations after meals, and damage to autonomic function. However, those with the same degree of weight loss as anorexia nervosa patients without mental symptoms do not show significant delayed emptying.

　　Fifth, diseases involving gastric smooth muscle

　　In addition to causing lesions in other systemic organs, such diseases often involve diffuse gastrointestinal smooth muscle, leading to dysfunction of intestinal motility. Although esophageal involvement is relatively common, the smooth muscle of the stomach can also be involved, causing gastroparesis. Progressive systemic sclerosis often occurs with delayed gastric emptying. The development process of gastrointestinal motility disorders in this disease includes two stages: initial nerve lesions and muscular lesions caused by myofibrous tissue infiltration.

　　Most patients with myotonic dystrophy have delayed gastric emptying of solid and liquid foods. The disease is characterized by increased tension and enhanced contraction activity in the duodenum and proximal jejunum, which is believed to be due to partial depolarization caused by smooth muscle damage. This theoretically increases the resistance to gastric emptying, leading to delayed gastric emptying.

　　Amyloidosis often involves the muscular layer of the gastrointestinal tract, causing motor dysfunction. In 1956, Intriere and Brown reported a case of primary amyloidosis that involved only the stomach. In addition to the involvement of the muscular layer, amyloid neuropathy and vascular lesions leading to intestinal ischemia are also important causes of gastrointestinal motility dysfunction. About 70% of primary and 55% of secondary amyloidosis occur with gastrointestinal symptoms.

　　Six, Gastroesophageal Reflux Disease

　　About 60% of patients with gastroesophageal reflux disease have delayed gastric emptying, and it is not yet clear whether this abnormality is primary or secondary.

　　Seven, Paraneoplastic Syndrome

　　In some patients with tumors, gastroparesis can be part of the paraneoplastic syndrome. Chinn et al. reported 7 cases of pulmonary carcinoid, of which 6 developed gastroparesis. Histological examination showed degeneration of the intermuscular plexus, reduction of neurons and axons, infiltration of inflammatory cells such as lymphocytes and plasma cells, and proliferation of glial cells, while the submucosal plexus was not affected.

　　Eight, Ischemic Gastroparesis

　　Libefrski et al. recently reported two cases of severe gastroparesis in patients with mesenteric artery occlusion and chronic gastrointestinal ischemia, accompanied by gastric electrical rhythm disorder and related symptoms. Six months after bypass vascular transplantation surgery, the patients' gastric solid emptying and gastric electrical rhythm returned to normal, and the symptoms also disappeared.

　　Nine, Idiopathic Gastroparesis

　　That is, idiopathic gastroparesis, accounting for about 50% of patients with delayed gastric emptying. These patients can be roughly divided into two groups: one group is diagnosed with functional dyspepsia, and the other group is affected by diffuse gastrointestinal smooth muscle, which has motility disorders throughout the gastrointestinal tract. In addition to gastroparesis, it often has multiple diagnoses such as irritable bowel syndrome or pseudo-obstruction.

　　1. Diabetic Gastroparesis (DGP) Patients with diabetes often have abnormal motility throughout the gastrointestinal tract.

　　2. Postoperative Gastroparesis Postoperative gastroparesis is common. The incidence of delayed gastric emptying after vagotomy is 5% to 10%, and after vagotomy with pyloroplasty, it is 28% to 40% for delayed gastric emptying of solids. Vagotomy of the vagus nerve trunk reduces the relaxation function of the gastric fundus, the contraction of the gastric antrum, and the coordinated relaxation function of the pylorus, leading to accelerated liquid emptying and delayed solid emptying. However, the highly selective (parietal cell) vagotomy can only prolong the delay in the emptying of solids without affecting the total gastric emptying.

　　3. Neurogenic Anorexia About 80% of patients with neurogenic anorexia have delayed gastric emptying of solids, but normal liquid emptying. Delayed gastric emptying is accompanied by gastric antrum motility rhythm disorder, low basal tension, decreased postprandial plasma norepinephrine and neurotensin concentrations, and autonomic nervous system dysfunction. However, there is no significant delay in emptying in individuals with the same degree of weight loss as neurogenic anorexia patients without psychiatric symptoms.

　　4. Diseases involving the gastric smooth muscle, in addition to causing lesions in other organs of the body, often involve diffuse gastrointestinal smooth muscle, leading to gastrointestinal motility dysfunction. Although esophageal involvement is relatively common, the smooth muscle of the stomach can also be affected, causing gastroparesis.

　　1. Low motility in the antrum of the stomach delays gastric emptying.

　　2. The reduced compliance of the proximal stomach weakens its capacity.

　　3. The pressure reduction in the proximal stomach decreases the emptying of gastric fluid.

　　4. The movement of the stomach, pylorus, and duodenum is not coordinated, so the main manifestation of this disease is delayed gastric emptying, with symptoms such as early satiety, upper abdominal fullness after meals, and discomfort in the upper abdomen after eating.

　　1. A low-fat, low-fiber diet should be given, with small and frequent meals, mainly in liquid form, to facilitate gastric emptying. Since smoking can slow down gastric emptying, smoking should be avoided. It is best to avoid using drugs that can delay gastric emptying. The symptoms of gastroparesis are often related to eating, and the symptoms are more obvious during or after meals. Some may appear when fasting. The vomit contains food eaten 4-6 hours ago, or it may be the food from the previous day. Therefore, regular eating is the basic therapy for diabetic gastroparesis, and patients should absolutely avoid eating too much. Meals should be timed and quantified daily, with an equal distribution of 1/3 of the meal amount for breakfast, lunch, and dinner.

　　1. In most cases, diabetes is one of the common causes of gastroparesis, caused by diabetic neuropathy, which damages the nerves that control gastrointestinal motility. It belongs to a gastrointestinal motility disorder and is also known as gastric paresis, gastric atony, gastric retention, etc. At least more than 50% of type 2 diabetic patients have diabetic gastroparesis, which often occurs in patients who have not been treated, are treated improperly, or are not treated regularly, among whom insulin-dependent diabetic patients are more common. 2. In most cases, diabetes is one of the common causes of gastroparesis, caused by diabetic neuropathy, which damages the nerves that control gastrointestinal motility. It belongs to a gastrointestinal motility disorder and is also known as gastric paresis, gastric atony, gastric retention, etc. At least more than 50% of type 2 diabetic patients have diabetic gastroparesis, which often occurs in patients who have not been treated, are treated improperly, or are not treated regularly, among whom insulin-dependent diabetic patients are more common.

　　1. Gastric Emptying Function Test

　　There are many methods to check the gastric emptying function. Currently, it is considered that radioactive isotope gastric emptying test should be the first choice. For patients with dyspepsia of unknown cause, if conditions permit, routine radioactive labeling of solid and liquid gastric emptying tests should be performed. This test is of great value for diagnosis and is also an important objective evaluation method for observing the efficacy of prokinetic drugs. The methods of intubation and barium meal or X-ray opaque markers are less commonly used due to many defects. Impedance technology can measure gastric liquid emptying and is likely to be widely used in the future. Ultrasound measurement of gastric emptying is currently only used as a research method due to high technical requirements.

　　2. Gastric Intraluminal Pressure

　　This examination is only performed when there is an abnormal gastric emptying test. In patients with gastroparesis, gastric intraluminal pressure can show abnormal gastric motility, with the most common being low motility in the antrum after meals. In patients with gastroparesis after partial gastrectomy, the measurement of near-end stomach static pressure shows low basic tension.

　　3. Gastroelectrography

　　Gastroelectrography is a non-invasive examination method. The basic electrical rhythm of the stomach is a slow wave potential of 3 times per minute, which determines the frequency and conduction direction of gastric muscle contraction. Once the slow wave potential disappears, the action potential of the stomach and the contraction of the stomach cannot occur. It has been found that various types of gastroparesis can occur with abnormal gastric electrical rhythm, such as tachygastria, bradygastria, and disordered gastric electrical rhythm. These abnormalities can lead to delayed gastric emptying. Some prokinetic drugs can restore normal function.

　　Patients with gastroparesis should be given a low-fat, low-fiber diet, eat less and more meals, and mainly consume liquid foods to facilitate gastric emptying. Since smoking can slow down gastric emptying, smoking should be avoided. It is recommended to eat more螺蛳、海带、紫菜、玳瑁、甲鱼、乌龟、海蜇、水蛇、薏米、菱、核桃、羊肾、猪腰、刀豆、沙虫、鲈鱼、鲐鱼.

　　1. General treatment

　　Patients with gastroparesis should be given a low-fat, low-fiber diet, eat less and more meals, and mainly consume liquid foods to facilitate gastric emptying. Since smoking can slow down gastric emptying, smoking should be avoided. It is best to avoid using drugs that can delay gastric emptying.

　　2. Treatment of primary diseases

　　For diabetic gastroparesis, it is best to control hyperglycemia as much as possible. Some patients may improve their symptoms due to controlled hyperglycemia. Supplementing adequate calories can improve gastric emptying in patients with neurogenic anorexia, and correcting mental disorders is also necessary for the complete recovery of symptoms. Malageleda et al. reported a case where the symptoms of gastroparesis disappeared after the resection of a pulmonary tumor, and the gastric motility returned to normal. As mentioned earlier, ischemic gastroparesis caused by chronic mesenteric artery occlusion can completely return to normal after vascular reconstruction.

　　3. Prokinetic drugs

　　The use of prokinetic drugs is currently the most effective treatment method for most patients with gastroparesis. Prokinetic drugs are a class of drugs that can restore, enhance, and coordinate the contraction activity of gastrointestinal smooth muscle, and accelerate the movement of intraluminal substances.

　　Carbamylmethylcholine can increase the frequency and amplitude of gastric contractions, but radioactive gastric emptying tests have shown that it cannot accelerate gastric emptying, so some people believe that the drug does not belong to prokinetic drugs.

　　Currently, commonly used prokinetic drugs include metoclopramide, domperidone, and cisapride, which can increase the frequency and amplitude of antral contractions, strengthen the coordination of antral duodenal contractions, and are used to treat various types of gastroparesis, accelerating gastric emptying and improving clinical symptoms. However, the long-term treatment effect of metoclopramide and domperidone is not very satisfactory, while cisapride still has good efficacy when used for a long time.

　　In recent years, the prokinetic effect of erythromycin has attracted more attention. Erythromycin, as a motilin receptor agonist, stimulates gastrointestinal motility and induces the stomach to produce a phase similar to the interdigestive MMC III phase after meals, causing strong contractions in the antrum, reducing pyloric pressure, improving the coordination of antral duodenal contractions, and promoting the emptying of solid foods (including undigested food particles).

　　In 1990, Janssens et al. were the first to use erythromycin to treat diabetic gastroparesis, achieving good short-term efficacy. In 1993, Richards et al. were the first to use erythromycin to treat idiopathic gastroparesis, also with good efficacy, and it was proven that erythromycin, whether administered intravenously, short-term oral administration (4 weeks), or long-term oral administration (1 to 11 months) for maintenance treatment, could increase gastric solid emptying, improve clinical symptoms, and had no significant side effects. Erythromycin also has good efficacy in the treatment of gastroparesis caused by neurogenic anorexia, vagotomy after surgery, progressive systemic sclerosis, and chemotherapy for cancer.

　　关于红霉素的用法：Camilleri主张先用3mg／kg体重静脉注射，每8小时1次，待患者能耐受进食后改为口服250mg，每日3次，一般不超过10日。能耐受红霉素的患者可持续用药数月，只要有益于症状改善且无副作用。

　　The usage of erythromycin: Camilleri advocates starting with an intravenous injection of 3mg/kg body weight every 8 hours, and changing to oral administration of 250mg three times a day after the patient can tolerate eating, generally not exceeding 10 days. Patients who can tolerate erythromycin can continue to take the drug for several months, as long as it is beneficial for symptom improvement and has no side effects.

　　The side effects of erythromycin include nausea, vomiting, diarrhea, etc. High doses can also cause ventricular tachycardia. Erythromycin can also cause subclinical presynaptic inhibition at the neuromuscular junction, exacerbating the condition of patients with myasthenia gravis. Long-term use of erythromycin also needs to consider the problem of induction of drug-resistant strains. The derivative of erythromycin, EM-523 and EM-574, has prokinetic effects but no antibacterial activity, which can solve this problem.

　　Motilin Peeters et al. used motilin intravenous infusion to treat 6 patients with severe diabetic gastric paresis, significantly accelerating the emptying of gastric fluid and solid. Therefore, motilin will be able to provide a new means for the treatment of gastric paresis in the future.

　　4. Surgical Treatment

　　Surgical treatment can be considered for a small number of refractory gastric paresis patients. There are reports that after partial gastrectomy and gastrojejunal anastomosis in some patients with idiopathic gastric paresis, symptoms were significantly relieved. Some patients with postoperative gastric paresis showed significant improvement after further extensive gastric resection and establishment of Roux-en-Y drainage. Yeung et al. reported a case of a diabetic patient who developed refractory gastric paresis after vagotomy and pyloroplasty for duodenal ulcer, leading to persistent nausea and vomiting, and the prokinetic drug therapy was ineffective. However, after undergoing percutaneous gastrostomy tube placement under X-ray fluoroscopy, long-term relief was achieved.

　　5. Other Therapies

　　Gastric pacing (Gastric Pacing) can restore the normal slow wave rhythm of disordered gastric electrical activity, thereby restoring normal gastric motility. Some people have tried it to treat postoperative gastric paresis with disordered gastric electrical rhythm, with some efficacy. However, its technical issues and its role in the treatment of gastric paresis need further study.